ReviewCancers2021
Interaction of Opioids with TLR4-Mechanisms and Ramifications.
Review in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- DAMPs and PAMPs in the Perioperative Period: Danger Signaling, Immune Dysfunction, and Oncologic Implications.Medicina (Kaunas, Lithuania) · 2026Review
- Neuropathic pain in traumatic brain injury: consequences, mechanisms, and therapeutic avenues.Inflammopharmacology · 2026Review
- Crosstalk Between Opioids and the Anti-Tumour Immune Checkpoint Axis.Current oncology (Toronto, Ont.) · 2026Review
- Opioid Signaling in Multiple Sclerosis: Emerging Targets for Repair.International journal of molecular sciences · 2026Review
- Unregulated Substance Abuse and Systemic Inflammation Markers: A Review.Healthcare (Basel, Switzerland) · 2026Review
- A study on the effect of remimazolam on cellular immune function during the perioperative period in older adults who are having laparoscopic surgery for colorectal cancer.Frontiers in oncology · 2026Article
- The Role of Toll-like Receptors and Viral Infections in the Pathogenesis and Progression of Pulmonary Arterial Hypertension-A Narrative Review.International journal of molecular sciences · 2025Review
- Low dose naloxone mitigates opioid tolerance and dependence and restores mesenchymal stem cell function for cell therapy in addiction.Scientific reports · 2025Article
- Prenatal opioid exposure and maternal HCV infection impair microglia development and function: A patient-specific in vitro model.Brain, behavior, and immunity · 2025Article
- Unveiling the therapeutic potential of octreotide in treating morphine dependence.Scientific reports · 2025Article
- Buprenorphine induces human fetal membrane sterile inflammation.Journal of reproductive immunology · 2025Article
- Peripartum buprenorphine and oxycodone exposure impair maternal behavior and increase neuroinflammation in new mother rats.Brain, behavior, and immunity · 2025Article
- Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.Frontiers in neuroscience · 2025Review
- Article
- From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System.International journal of molecular sciences · 2024Review
- Photo-affinity and Metabolic Labeling Probes Based on the Opioid Alkaloids.Chembiochem : a European journal of chemical biology · 2024Article
- Methadone Requires the Co-Activation of μ-Opioid and Toll-Like-4 Receptors to Produce Extracellular DNA Traps in Bone-Marrow-Derived Mast Cells.International journal of molecular sciences · 2024Article
- Disinhibition does not play a role in endomorphin-2-induced changes in inspiratory motoneuron output produced by in vitro neonatal rat preparations.Respiratory physiology & neurobiology · 2024Article
- Fentanyl enhances immune cell response through TLR4/MD-2 complex.Frontiers in pharmacology · 2024Article
- Chemical tools for the opioids.Molecular and cellular neurosciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The innate immune receptor toll-like receptor 4 (TLR4) is known as a sensor for the gram-negative bacterial cell wall component lipopolysaccharide (LPS). TLR4 activation leads to a strong pro-inflammatory response in macrophages; however, it is also recognised to play a key role in cancer. Recent studies of the opioid receptor (OR)-independent actions of opioids have identified that TLR4 can respond to opioids. Opioids are reported to weakly activate TLR4, but to significantly inhibit LPS-induced TLR4 activation. The action of opioids at TLR4 is suggested to be non-stereoselective, this is because OR-inactive (+)-isomers of opioids have been shown to activate or to inhibit TLR4 signalling, although there is some controversy in the literature. While some opioids can bind to the lipopolysaccharide (LPS)-binding cleft of the Myeloid Differentiation factor 2 (MD-2) co-receptor, pharmacological characterisation of the inhibition of opioids on LPS activation of TLR4 indicates a noncompetitive mechanism. In addition to a direct interaction at the receptor, opioids affect NF-κB activation downstream of both TLR4 and opioid receptors and modulate TLR4 expression, leading to a range of in vivo outcomes. Here, we review the literature reporting the activity of opioids at TLR4, its proposed mechanism(s), and the complex functional consequences of this interaction.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.